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A population pharmacokinetic model based on HPTN 077 of long‐acting injectable cabotegravir for HIV PrEP
Author(s) -
Yu Yifan,
Bigos Kristin L.,
Marzinke Mark A.,
Landovitz Raphael J.,
McCauley Marybeth,
Ford Susan,
Hendrix Craig W.,
Bies Robert R.,
Weld Ethel D.
Publication year - 2022
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.15477
Subject(s) - pharmacokinetics , emtricitabine , population , human immunodeficiency virus (hiv) , intramuscular injection , pharmacology , medicine , antiretroviral therapy , immunology , viral load , environmental health
Aims Cabotegravir delivered as a long‐acting intramuscular injection has shown superior efficacy to oral tenofovir‐emtricitabine as pre‐exposure prophylaxis (PrEP) for HIV. Cabotegravir pharmacokinetics (PK), like those of other long‐acting depot preparations, exhibit variability between individuals and between injection occasions. The aim of this study is to describe the population pharmacokinetics of long‐acting cabotegravir (CAB‐LA). Methods Using available PK measurements from 133 participants in the HIV Prevention Trials Network (HPTN) 077 trial, we analysed CAB‐LA PK data using nonlinear mixed‐effects modelling to develop a population PK model. Results A two‐compartment model with first order absorption best described the CAB‐LA PK. The analysis identified between‐occasion variability (BOV, i.e., differences in PK within one individual from one injection to the next) as a significant covariate affecting the absorption rate, with an estimated contribution of BOV to PK variability on the absorption rate (k a ) of 38.5%. Sex and body weight were identified as significant covariates influencing the absorption rate and apparent clearance of CAB‐LA after intramuscular injection at various doses and frequencies. Male participants had 67% higher k a than female participants. Serially adding to the model body weight on clearance, sex on k a , and BOV on k a led to a decrease in the objective function value (OFV) of 24.4, 36 and 321.4, respectively. Conclusion The public availability of this model will facilitate and enable a wide variety of future clinically relevant simulations to inform the optimal use of CAB‐LA.